Renal impairment is more likely to be reversible with supportive measures alone when it is not related to cast formation [3]. There are a number of factors that can contribute to the development of AKI in MM; these include dehydration, hypercalcaemia, and the ingestion of nephrotoxic drugs [6]. Qureshi A, Tariq MJ, Shah Z, Abu Zar M, Aslam S, Rafae A, Shafqat M, Malik MN, Faisal MS, Anwer F. J Community Hosp Intern Med Perspect.
Van Staa TP, Leufkens HG, Abenhaim L, Zhang B, Cooper C. J Bone Miner Res. Finally, let’s move onto pathology. After endocytosis the FLCs undergo vesicular trafficking, which is dependent upon acidification of the vesicle. The tubular cast leads to an inflammatory reaction and often a giant, multinucleated cells can be observed surrounding the cast within the tubule (also known as a foreign body reaction).
| 2005 Apr;20(4):564-70. doi: 10.1359/JBMR.041218. These initial results have led to the development of EuLITE, a randomised controlled trial of HCO dialysis versus conventional dialysis in patients with de novo MM, biopsy proven cast nephropathy, and dialysis-dependent acute kidney injury at presentation. Saad F, Lipton A, Cook R, Chen YM, Smith M, Coleman R. Pathologic fractures correlate with reduced survival in patients … We are committed to sharing findings related to COVID-19 as quickly as possible. also considered the renal outcomes of patients treated with Bortezomib; in their study it was used as part of a BDD (Bortezomib, doxorubicin, and dexamethasone) regimen; they enrolled 68 patients with light-chain-induced renal failure (defining acute renal failure as a recent decline in glomerular filtration rate (GFR) <50 mLs/min where other causes of renal failure had been clinically excluded) [37]. Case 21 Physical Exam More recently Thalidomide use has been reported in larger numbers of patients who have been dialysis dependent at presentation; in a study of high cut off haemodialysis 14/19 patients received Thalidomide and recovered renal function [27]. Whilst it is self-evident that an agent that rapidly reduces tumour burden should also result in an improvement in renal outcome, little work has been done to specifically address this question. Finkel KW, Cohen EP, Shirali A, Abudayyeh A: Paraprotein–Related Kidney Disease: Evaluation and Treatment of Myeloma Cast Nephropathy. The dynamics of serum FLC (sFLC) levels and renal clearance is important for the interrelationship between FLC processing by PTEC and the development of cast nephropathy.
Uromodulin has been shown to have a specific binding site for FLC; this has been shown in animal models to be a peptide sequence [23].
Uromodulin may also have an immunomodulatory role via the induction of inflammatory cytokines such as TNF-α and IL-6 from monocyte/macrophages and neutrophils [25, 26]. Monoclonal gammopathy of undetermined significance, multiple myeloma, and osteoporosis. NephSIM: A free, mobile-optimized, nephrology teaching tool, Diagnosis: Myeloma cast nephropathy or light chain cast nephropathy. Please enable it to take advantage of the complete set of features! A. Pineda, P. C. O'Brien, and K. E. Holley, “Treatment of renal failure associated with multiple myeloma. In addition to an evolution in the chemotherapy options for patients with AKI and MM, there has been a recent reevaluation of the role of extracorporeal removal of sFLC. Kidney biopsy specimens showed features of cast nephropathy with PAS- and silver-negative casts with a fractured appearance sur-rounded by an interstitial infiltrate. All these factors have the potential to trigger the development of cast nephropathy, which is the commonest cause of severe AKI. 1999 May;42(5):882-90. doi: 10.1002/1529-0131(199905)42:5<882::AID-ANR6>3.0.CO;2-C. Bouvard B, Royer M, Chappard D, Audran M, Hoppé E, Legrand E. Joint Bone Spine. Renal failure is highly significant in myeloma, as patient survival can be stratified by the severity of the renal impairment. T. Eriksson, S. Björkman, and P. Höglund, “Clinical pharmacology of thalidomide,”, T. Eriksson, P. Höglund, I. Turesson et al., “Pharmacokinetics of thalidomide in patients with impaired renal function and while on and off dialysis,”, P. G. Richardson, E. Blood, C. S. Mitsiades et al., “A randomized phase 2 study of lenalidomide therapy for patients with relapsed or relapsed and refractory multiple myeloma,”, M. Dimopoulos, A. Spencer, M. Attal et al., “Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma,”, D. M. Weber, C. Chen, R. Niesvizky et al., “Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America,”, S. V. Rajkumar, S. R. Hayman, M. Q. J Bone Miner Res. Of particular interest in this study was the observation that there was an early and sustained reduction of sFLC levels in those patients who recovered kidney function; those patients who had early interruptions in chemotherapy did not have early reductions in FLC levels and usually did not recover independent kidney function [27]. There were several design shortfalls in the study; these included the absence of histological diagnosis of cast nephropathy and the presence of dialysis dependency at randomisation in only 28% of those recruited [55].
The gamma gap, or protein gap, is the difference between the total protein and serum albumin of more than 4 g/dL. These and other studies show that monoclonal FLCs have a greater inflammatory effect on PTECs than other freely filtered proteins [14, 17]. A man aged 41 years presented to us with a lytic lesion in the proximal humerus and developed a pathological fracture which was managed with nailing (figure 1). Case 21 Introduction In monoclonal gammopathies like multiple myeloma, the secretion of a positively charged monoclonal protein can lead to a low anion gap. So if there’s so much proteinuria, why was the urinalysis negative for protein? Another way to measure both albumin and non-alubmin proteinuria is the urine protein sulfosalicylic acid (SSA) precipitation test.
There is no evidence to date that endocytosis of polyclonal FLC activates PTEC; however there is substantial data that show a profound proinflammatory and cytotoxic potential of monoclonal FLC. At presentation at least 50% of patients will have AKI of a variable degree, and around 10% have severe AKI from which they will die within weeks unless they are treated with renal replacement therapy by dialysis [3].
NLM Our patient had 6 g of proteinuria per day – a value of more than 1 g of free light chains/day in the urine should raise suspicion for myeloma kidney. Osteoporotic fractures seem to be less of a problem in these patients. To confirm monoclonality, we can use immunofluorescence (IF) to stain for kappa and lambda. There have now been many large studies investigating the use of Bortezomib, initially in relapsed/refractory MM and more recently in de novo MM. It is important to note that the number of patients with histological evidence of cast nephropathy was small; only six patients had had a renal biopsy (of whom two were not enrolled because of a diagnosis of amyloid), and the numbers requiring dialysis at the outset and the end were also not reported. As it progresses, bone pain, bleeding, frequent infections, and anemia may occur. In a population-based retrospective cohort study, 165 Olmsted County, MN, residents with myeloma diagnosed from 1945 to 2001 (55% men; mean age, 70.7 +/- 11.1 years) were followed for 537 person-years. COVID-19 is an emerging, rapidly evolving situation. USA.gov. 2020. Renal failure is highly significant in myeloma, as patient survival can be stratified by the severity of the renal impairment. eCollection 2020 Feb. Case Rep Hematol. They enrolled 20 patients (two who were dialysis dependent) with a serum creatinine of ≥130 μmol/l and defined renal recovery as achieving a serum creatinine of <130 μmol/l [38]. Bortezomib is a proteasome inhibitor that is the first in class, and it was synthesised in 1995 and was first used in humans until 1999. Subsequently, Chen et al. Other studies of PE have shown conflicting results, but these are all limited by small sample sizes and other methodological flaws [56, 57]. There is a differential capacity of any given clone of FLC to activate PTEC to produce proinflammatory cytokines through activation of NFκB; this may contribute to the inflammatory cell infiltration and accelerated fibrosis that is seen in cast nephropathy [14]. The urinalysis is most sensitive albuminuria (and may not pick up non-albumin proteinuria, like immunoglobulin light chains). For patients on dialysis there was a substantial decrease in trough concentrations postdialysis, indicating that an extradose is needed following dialysis treatment [50]. 2011, Article ID 493697, 9 pages, 2011. https://doi.org/10.1155/2011/493697, 1Renal Institute of Birmingham, University Hospital Birmingham, Birmingham B15 2TH, UK, 2Department of Nephrology, University Hospital Birmingham, Birmingham B15 2TH, UK, 3School of Immunity and Infection, University of Birmingham, Birmingham, B15 2TT, UK. 2005; 20:487–493.
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